AN INTRESTING CASE OF END STAGE RENAL DISEASE DEPARTMENT OF NEPHROLOGY APOLLO HOSPITALS, CHENNAI.

1. AN INTRESTING CASE OF END STAGE RENAL DISEASE DEPARTMENT OF NEPHROLOGY APOLLO HOSPITALS, CHENNAI.

2. 63 YEARS MALE PATIENT “KB” K/C/O, • DIABETES MELLITUS--- 20years, • HYPERTENSION---16years, • ISCHEMIC HEART DISEASE,(post CABG- 2001) - COPD,(chronic smoker)

3. He is a case of End stage Renal disease due to Diabetic Nephropathy on regular Haemodialysis Since March-2008.

4. He presented to us in last week of Febraury with, • Pain in lower abdomen during haemodialysis for 10 days. • Pain in right shoulder and right hip joint for one week. • Erythematous lesions with itching on lower limbs.

5. On Examination:- Elderly male, Hypertensive, Vitals- Stable. Skin:- Erythematous, raised non-tender, multiple lesions on lower limbs as well on the back and chest wall. Systemic examination was normal.

6. CLINICAL DIAGNOSIS, Pain in Abdomen:- ? Mesentric ischemia, (DM,HTN, SMOKER, IHD,ESRD) ? Pancreatitis. Erythematous lesions:- ? Drug reaction, ?cause, (was on haemodialysis elsewere)

7. Blood Biochemistry, • As a routine practice before haemodialysis, blood was collected for IDNAT(HIV, Hepatitis B, Hepatitis C). • Hepatitis B was positive,(?acute seroconversion) • SGPT and Alkaline phosphatase was high, • Sr.PTH was high(mineral bone disease), • Sr.Amylase and Sr.Lipase was normal( ruled out pancreatitis) • Ejection fraction was normal.

8. Ig M Anti HbC was positive, ( he had acute Hepatitis B virus infection) HBV viral load was:- 14,501,379. (High) ANA + was positive,(? False positive) ANCA, dsDNA were negative.

9. During the course in the hospital, • He continued to have pain in abdomen during Haemodialysis,(? Mesentric ischemia) which used to subside after reducing blood pump speed. • Skin lesions persisted. • Pain in right shoulder and hip persisted.

10. CT Abdomen with angiography, failed to reveal any obstruction to mesentric blood flow. • Ultrasound of right shoulder and right thigh showed, Localized hematoma. ? Anticoagulation during haemodialysis, ? Cause.

11. He was subjected to skin biopsy,

12. SKIN BIOPSY

15. IMMUNOFLUORESCENCE:- Significant deposits of IgA, C3c,IM and fibrinogen in dermal vessels consistent with vasculitis.

17. DIAGNOSIS ?

18. Diagnosis was strongly favoring Extra renal manifestations of Hepatitis B virus infection.

19. Diagnosis, • ESRD with DN, • Extra renal, extra hepatic manifestation of Acute Hepatitis B virus infection(vasculitis). • Mesentric ischemia.(? Vasculitis induced) • Haematoma of right pectoralis major and thigh. (?Anticoagulation, ?Vasculitis induced)

20. Therapy, • Haemodialysis (Heparin free,low pump speed), • ?Steroids,(initiated on oral steroids) • ?Cytotoxic drugs, • Lamivudine.

21. DISCHARGED

22. FOUR days later, • Pain during haemodialysis reduced considerably, • Skin lesions reduced considerably, although lesion at nape of neck and chest wall got ulcerated. • Developed severe proximal muscle weakness of both upper and lower limbs.

23. HEALING SKIN LESIONS AFTER TREATMENT

24. On Examination, • Power of proximal muscles was II/V, • Power of distal muscles was IV/V.

25. We suspected, • Steroid toxicity, • Spectrum of Hepatitis B virus infection, - ?GBS(demylenating polyradiculoneuropathy) - ?PAN, - ?Myositis.

26. BLOOD BIOCHEMISTRY:- CPK:- 1980, (high) Sr.Aldolase:- 22.8,(high) NCV studies:- Bilateral symmetric sensory motor polyradiculoneuropathy. ? Diabetic polyneuropathy, ? Vasculitic.

27. DAY 2 of admission:- • Continued to have severe weakness of both upper and lower limbs. • Subjected to muscle biopsy.

28. MUSCLE BIOPSY

29. Focal degeneration and regeneration is seen. • Few ghost fibres. • Large hypertrophied fibres are not seen. • No perivascular inflamation. • Features consistent with destuctive myopathy.

32. IMMUNOSUPPRESION?

33. Ing. Methylprednisolone 1gm pulse, six doses • Ing. Cyclophosphamide.

34. COURSE:- Following higher doses of steroids and cytotoxic drug his power improved considerably. We continued him on oral steroids. He is on regular haemodialysis, has no pain during haemodialysis, skin lesions had healed, and muscle power has improved considerably.

35. EXTRA HEPATIC MANIFESTATION OF HEPATITIS B. (REVIEW)

36. Approximately 400 million people are chronic HBV carriers worldwide. • The spectrum of chronic HBV infection ranges from asymptomatic hepatitis B surface antigen carrier state to chronic hepatitis with progression to cirrhosis and end-stage liver disease. • Several extrahepatic syndromes are associated with chronic HBV infection.

38. HBV serum sickness-like syndrome, • A serum sickness-like syndrome may occur in 10 to 25% of patients in the early prodrome of acute HBV hepatitis. • Fever, maculopapular or urticarial rash. • Transient arthralgias and/or arthritis involving distal and large joints of the extremities are common.

39. HBV associated polyarteritis nodosa (HBV-PAN)

40. The initial presentation is similar to the serum sickness-like syndrome and includes fever, arthralgias, urticaria, and palpable purpura. • Unlike the prodromal serum sickness syndrome which resolves spontaneously, in HBV-PAN a frank vasculitis develops over several weeks and may involve virtually any organ.

41. Abdominal pain secondary to mesenteric ischemia. • Mononeuritis multiplex secondary to involvement of the vasa nervorum of peripheral nerves. • Myocardial ischemia from coronary artery involvement. • Renal involvement may present as renin-dependent hypertension, microscopic hematuria, non-nephrotic or nephrotic proteinuria, or even renal failure.

42. Pathology:- HBV-PAN consists of focal inflammation of the small and medium sized arteries. The inflammation is panmural, characterized by fibrinoid necrosis, leukocyte infiltration, fibrin deposition, and occasional aneurysm formation

43. Pathogenesis of the serum sickness and vasculitis syndromes

44. Mechanism of extrahepatic syndromes appears to be immune-mediated. • Deposition of circulating immune complexes, • Induction of local immune complex formation by viral antigens, • Reaction with tissue antigens by viral-induced autoantibodies, • Direct viral reaction to extrahepatic tissue sites.

45. DIAGNOSIS:-

46. Skeletal muscle, peripheral nerve biopsy. • Angiography- saccular or fusiform aneurysms. • Renal angiography has the highest diagnostic yield.

47. Polyarteritis Nodosa with Fibrinoid Necrosis

48. Dermal Vasculitis

49. Vasculitis of Interlobar Artery of the Kidney

50. Treatment of Hepatitis B Virus associated -PAN